Anti-Inflammatory Actions of G-Protein-Coupled Estrogen Receptor 1 (GPER) and Brain-Derived Estrogen Following Cerebral Ischemia in Ovariectomized Rats
Global cerebral ischemia can elicit rapid innate neuroprotective mechanisms that protect against delayed neuronal death. Brain-derived 17β-estradiol (BDE2), an endogenous neuroprotectant, is synthesized from testosterone by the enzyme aromatase (Aro) and is upregulated by brain ischemia and inflamma...
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MDPI AG
2023-01-01
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| Online Access: | https://www.mdpi.com/2079-7737/12/1/99 |
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| author | Jing Xu Jing Bai Fujia Gao Chao Xu Yuanyuan Huang Danyang Li Lu Wang Ruimin Wang |
| author_facet | Jing Xu Jing Bai Fujia Gao Chao Xu Yuanyuan Huang Danyang Li Lu Wang Ruimin Wang |
| author_sort | Jing Xu |
| collection | DOAJ |
| description | Global cerebral ischemia can elicit rapid innate neuroprotective mechanisms that protect against delayed neuronal death. Brain-derived 17β-estradiol (BDE2), an endogenous neuroprotectant, is synthesized from testosterone by the enzyme aromatase (Aro) and is upregulated by brain ischemia and inflammation. Our recent study revealed that G1, a specific G-protein-coupled estrogen receptor 1 (GPER) agonist, exerts anti-inflammatory and anti-apoptotic roles after global cerebral ischemia (GCI). Herein, we aimed to elucidate whether G1 modulates the early inflammatory process and the potential underlying mechanisms in the ovariectomized rat hippocampal CA1 region. G1 was found to markedly reduce pro-inflammatory (iNOS, MHCII, and CD68) and to enhance anti-inflammatory (CD206, Arginase 1, IL1RA, PPARγ, and BDNF) markers after 1 and 3 days of reperfusion after GCI. Intriguingly, the neuroprotection of G1 was blocked by the Aro inhibitor, letrozole. Conversely, the GPER antagonist, G36, inhibited Aro-BDE2 signaling and exacerbated neuronal damage. As a whole, this work demonstrates a novel anti-inflammatory role of GPER, involving a synergistic mediation with BDE2 during the early stage of GCI. |
| first_indexed | 2024-03-09T13:31:41Z |
| format | Article |
| id | doaj.art-effac5469a114437986ad0f46668767b |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-09T13:31:41Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-effac5469a114437986ad0f46668767b2023-11-30T21:17:21ZengMDPI AGBiology2079-77372023-01-011219910.3390/biology12010099Anti-Inflammatory Actions of G-Protein-Coupled Estrogen Receptor 1 (GPER) and Brain-Derived Estrogen Following Cerebral Ischemia in Ovariectomized RatsJing Xu0Jing Bai1Fujia Gao2Chao Xu3Yuanyuan Huang4Danyang Li5Lu Wang6Ruimin Wang7Dementia and Dyscognitive Key Laboratory, Tangshan 063210, ChinaDementia and Dyscognitive Key Laboratory, Tangshan 063210, ChinaDementia and Dyscognitive Key Laboratory, Tangshan 063210, ChinaDementia and Dyscognitive Key Laboratory, Tangshan 063210, ChinaDementia and Dyscognitive Key Laboratory, Tangshan 063210, ChinaDementia and Dyscognitive Key Laboratory, Tangshan 063210, ChinaDementia and Dyscognitive Key Laboratory, Tangshan 063210, ChinaDementia and Dyscognitive Key Laboratory, Tangshan 063210, ChinaGlobal cerebral ischemia can elicit rapid innate neuroprotective mechanisms that protect against delayed neuronal death. Brain-derived 17β-estradiol (BDE2), an endogenous neuroprotectant, is synthesized from testosterone by the enzyme aromatase (Aro) and is upregulated by brain ischemia and inflammation. Our recent study revealed that G1, a specific G-protein-coupled estrogen receptor 1 (GPER) agonist, exerts anti-inflammatory and anti-apoptotic roles after global cerebral ischemia (GCI). Herein, we aimed to elucidate whether G1 modulates the early inflammatory process and the potential underlying mechanisms in the ovariectomized rat hippocampal CA1 region. G1 was found to markedly reduce pro-inflammatory (iNOS, MHCII, and CD68) and to enhance anti-inflammatory (CD206, Arginase 1, IL1RA, PPARγ, and BDNF) markers after 1 and 3 days of reperfusion after GCI. Intriguingly, the neuroprotection of G1 was blocked by the Aro inhibitor, letrozole. Conversely, the GPER antagonist, G36, inhibited Aro-BDE2 signaling and exacerbated neuronal damage. As a whole, this work demonstrates a novel anti-inflammatory role of GPER, involving a synergistic mediation with BDE2 during the early stage of GCI.https://www.mdpi.com/2079-7737/12/1/99global cerebral ischemiaG-protein-coupled estrogen receptor 1aromatasebrain-derived estrogeninflammation |
| spellingShingle | Jing Xu Jing Bai Fujia Gao Chao Xu Yuanyuan Huang Danyang Li Lu Wang Ruimin Wang Anti-Inflammatory Actions of G-Protein-Coupled Estrogen Receptor 1 (GPER) and Brain-Derived Estrogen Following Cerebral Ischemia in Ovariectomized Rats Biology global cerebral ischemia G-protein-coupled estrogen receptor 1 aromatase brain-derived estrogen inflammation |
| title | Anti-Inflammatory Actions of G-Protein-Coupled Estrogen Receptor 1 (GPER) and Brain-Derived Estrogen Following Cerebral Ischemia in Ovariectomized Rats |
| title_full | Anti-Inflammatory Actions of G-Protein-Coupled Estrogen Receptor 1 (GPER) and Brain-Derived Estrogen Following Cerebral Ischemia in Ovariectomized Rats |
| title_fullStr | Anti-Inflammatory Actions of G-Protein-Coupled Estrogen Receptor 1 (GPER) and Brain-Derived Estrogen Following Cerebral Ischemia in Ovariectomized Rats |
| title_full_unstemmed | Anti-Inflammatory Actions of G-Protein-Coupled Estrogen Receptor 1 (GPER) and Brain-Derived Estrogen Following Cerebral Ischemia in Ovariectomized Rats |
| title_short | Anti-Inflammatory Actions of G-Protein-Coupled Estrogen Receptor 1 (GPER) and Brain-Derived Estrogen Following Cerebral Ischemia in Ovariectomized Rats |
| title_sort | anti inflammatory actions of g protein coupled estrogen receptor 1 gper and brain derived estrogen following cerebral ischemia in ovariectomized rats |
| topic | global cerebral ischemia G-protein-coupled estrogen receptor 1 aromatase brain-derived estrogen inflammation |
| url | https://www.mdpi.com/2079-7737/12/1/99 |
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